title: Fatty acid profiles in Leishmania spp. isolates with natural resistance to nitric oxide and trivalent antimony.
abstract: Fatty acids, especially those from phospholipids (PLFA), are essential membrane components that are present in relatively constant proportions in biological membranes under natural conditions. However, under harmful growth conditions, such as diseases, environmental changes, and chemical exposure, the fatty acid proportions might vary. If such changes could be identified and revealed to be specific for adverse situations, they could be used as biomarkers. Such biomarkers could facilitate the identification of virulence and resistance mechanisms to particular chemotherapeutic agents. Therefore, specific biomarkers could lead to better therapeutic decisions that would, in turn, enhance treatment effectiveness. The objective of this study was to compare the fatty acid profiles of trivalent antimony and nitric oxide (NO)-resistant and -sensitive Leishmania chagasi and Leishmania amazonensis isolates. Fatty acid methyl esters (FAMEs) were obtained from total lipids (MIDI), ester-linked lipids (ELFA), and ester-linked phospholipids (PLFA). FAMEs were analyzed by chromatography and mass spectrometry. Species- or resistance-associated differences in FAME profiles were assessed by nonmetric multidimensional scaling, multiresponse permutation procedures, and indicator species analyses. The isolate groups had different MIDI-FAME profiles. However, neither the ELFA nor PLFA profiles differed between the sensitive and resistant isolates. Levels of the fatty acid 18:1 Δ9c were increased in sensitive isolates (p < 0,001), whereas the fatty acid 20:4 Δ5,8,11,14 showed the opposite trend (p < 0.01). We conclude that these two fatty acids are potential biomarkers for NO and antimony resistance in L. chagasi and L. amazonensis and that they could be helpful in therapeutic diagnoses.
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Sergipe (UFS), Av. Marechal Rondon, S/N, 49100-000, São Cristóvão, Sergipe, Brazil.
authors.forename: Alana Freire
authors.initials: AF
authors.lastname: de Azevedo
authors.forename: Jorge Luís de Lisboa
authors.initials: JL
authors.lastname: Dutra
authors.forename: Micheli Luize Barbosa
authors.initials: ML
authors.lastname: Santos
authors.forename: Darlisson de Alexandria
authors.initials: Dde A
authors.lastname: Santos
authors.forename: Péricles Barreto
authors.initials: PB
authors.lastname: Alves
authors.forename: Tatiana Rodrigues
authors.initials: TR
authors.lastname: de Moura
authors.forename: Roque Pacheco
authors.initials: RP
authors.lastname: de Almeida
authors.forename: Marcelo Ferreira
authors.initials: MF
authors.lastname: Fernandes
authors.forename: Ricardo
authors.initials: R
authors.lastname: Scher
authors.forename: Roberta Pereira Miranda
authors.initials: RP
authors.lastname: Fernandes
mesh_terms: D000965:Antimony / Q000494:pharmacology*; D015415:Biomarkers / Q000737:chemistry; D004351:Drug Resistance; D005227:Fatty Acids / Q000737:chemistry*; D007891:Leishmania / Q000737:chemistry* / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D010743:Phospholipids / Q000737:chemistry
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D010743:Phospholipids; D009569:Nitric Oxide; D000965:Antimony